Uterine leiomyomas (fibroids or myomas) are diagnosed in one-fourth of all women and up to 75 % of black women. The direct health care costs attributable to leiomyomas exceed $2.1 billion annually. However, our work and that of others, report that indirect costs (disability and absenteeism) are a large part of total costs for women with uterine fibroids. Addressing the symptoms of clinically significant uterine fibroids and controlling health care costs from a societal perspective are both important goals. Despite the prevalence and morbidity of this disease and the significant costs of treatment, there is a dearth of evidence to guide therapy. Two minimally-invasive FDA-approved techniques treat leiomyomas in a wide variety of sizes and locations: uterine artery embolization (UAE) and MRI-guided focused ultrasound surgery (MRgFUS). However, they differ significantly in approach, mechanism of action and side effects and they have never been directly compared. We therefore propose the FIRSTT trial: Fibroid Interventions: Reducing Symptoms Today and Tomorrow), a randomized clinical trial treating 220 women with symptomatic uterine leiomyomas with UAE or MRgFUS and following them for three years. A racially diverse cohort of subjects will be achieved by recruiting through Mayo Clinic Rochester and Duke University. This trial is powered to compare short- and long-term outcomes, adverse events, predictors of outcome, and costs of each treatment. The specific aims of this project are: 1) To report comprehensive outcomes and predictors of outcome following UAE and MRgFUS. 2) To quantitate and compare the ovarian impairment following UAE and MRgFUS. 3) To produce an economic analysis of UAE and MRgFUS treatment from a U.S. societal perspective. PUBLIC HEALTH RELEVANCE: Uterine leiomyomas or fibroids are found in one-fourth of all women and up to three-fourths of black women. Fibroids are the leading cause of hysterectomy and account for health care costs over $2.1 billion annually. This study proposes to study the outcomes and limitations of two widely used alternatives to hysterectomy for fibroids: uterine artery embolization (UAE) and magnetic resonance imaging guided focused ultrasound surgery (MRgFUS).